Our goal is to understand the interactions between regenerating motor nerves and microvessels in skeletal muscle. During embryonic development and postnatal growth, blood vessels and nerves interact to promote growth, differentiation, and direct patterning. Several growth factors once studied for their roles in either neural or vascular systems are now know to be active in both. Remarkably, however, the interaction between motor nerves and microvessels within skeletal muscle is poorly understood. Specific aims of this application are to: (1) Determine the effect of motor nerve regeneration on microvasculature topology and (2) Determine the effect of microvascular regeneration on motor nerve topology. Using transgenic mice that express spectral variants of fluorescent protein in motor nerves and blood vessels, these respective systems are selectively disrupted using microsurgery. Fluorescence microscopy is used to define and quantify the reorganization, distribution, and interactions between motor nerves and microvessels during degeneration, regeneration, and remodeling. These experiments will provide critical new insight into fundamental interactions between motor nerves and the vascular supply of skeletal muscle. Overall, we intend to provide a novel foundation for the preservation of skeletal muscle function and to enhance the treatment of patients suffering from the debilitating effects of aging, disuse, and disease.